Migration of Norway rats resulted in the worldwide distribution of Seoul hantavirus today

Abstract

Despite the worldwide distribution, most of the known Seoul viruses (SEOV) are closely related to each other. In this study, the M and the S segment sequences of SEOV were recovered from 130 lung tissue samples (mostly of Norway rats) and from six patient serum samples by reverse transcription-PCR. Genetic analysis revealed that all sequences belong to SEOV and represent 136 novel strains. Phylogenetic analysis of all available M and S segment sequences of SEOV, including 136 novel Chinese strains, revealed four distinct groups. All non-Chinese SEOV strains and most of the Chinese variants fell into the phylogroup A, while the Chinese strains originating from mountainous areas clustered into three other distinct groups (B, C, and D). We estimated that phylogroup A viruses may have arisen only within the last several centuries. All non-Chinese variants appeared to be directly originated from China. Thus, phylogroup A viruses distributed worldwide may share a recent ancestor, whereas SEOV seems to be as diversified genetically as other hantaviruses. In addition, all available mitochondrial DNA (mtDNA) sequences of Norway rats, including our 44 newly recovered mtDNA sequences, were divided into two phylogenetic groups. The first group, which is associated with the group A SEOV variants, included most of rats from China and also all non-Chinese rats, while the second group consisted of a few rats originating only from mountain areas in China. We hypothesize that an ancestor of phylogroup A SEOV variants was first exported from China to Europe and then spread through the New World following the migration of Norway rats.

Fig 1

Phylogenetic relationships between Seoul viruses (SEOV) detected or isolated in and outside China. ML/Bayesian trees were based on the S segment sequences (A), and ML/Bayesian trees were based on the M segment sequences (B). Numbers (>50%/>0.5) above or below branches indicate bootstrap values or posterior node probabilities. Thottapalayam virus (TPMV) was used as the outgroup. The SEOV strains in groups A, B, C, and D are shown in red, blue, green, and purple, respectively. The SEOV strains of group A outside China are shown in yellow. Sequences obtained in the present study are indicated in boldface. The scale bar represents the genetic distance. Aa, Apodemus agrarius; Rn, Rattus norvegicus; Rr, Rattus rattus; Rf, Rattus flavipectus; Cb, Cricetulus barabensis; Ct, Cricetulus tyiton; Mm, Mus musculus. These abbreviations represent the same species of host in Table S1 in the supplemental material.

Fig 2

Geographic distribution of SEOV variants found in China. The phylogroups and clusters of SEOV are consistent with those in Fig. 1. Sequences recovered in the present study, retrieved from GenBank (the accession numbers are given in Tables S1 and S2 in the supplemental material), and from previous studies (26, 27, 56, 60, 63, 71) were used for the map.

Fig 3

Inferred migration graph for SEOV in China (A) and around the world (B) and its reflection of the vents reconstructed from the MCC tree. The maps are based on satellite pictures made available in Google Earth (http://earth.google.com; doi:10.1371/journal.pcbi.1000520.g007).

Fig 4

Phylogenetic relationships between Norway rats captured in and outside China. The Bayesian tree was constructed with mtDNA sequences of cytochrome b. The sequences of Suncus murinus were used as the outgroup. The groups A and B are shown in red and blue, respectively. The GenBank accession numbers of the rat mtDNA sequences recovered outside China are shown in yellow. The scale bar represents the genetic distance.

Fig 5

Tanglegram constructed with the TreeMap program, showing SEOV variants and their rat carriers in China. The host tree on the left was based on cytochrome b sequences, and the hantavirus tree on the right was based on the complete S segment sequences. MrBayes v3.1.2 was used to construct the phylogenetic trees using the Bayesian method. The two trees were rooted with Suncus muinus and TPMV as outgroups, respectively.